The research proposed herein attempts to resolve the effects induced by the presence of a heavy-metal ion on the chemical properties of nucleotides and nucleotidyl coenzymes. This will be accomplished by utilizing a series of stable ruthenium-nucleotide complexes already prepared in this laboratory and by synthesizing additional compounds with other heavy-metal ions in which the metal is firmly coordinated to the base moiety. The use of these stable complexes provides the experimental system for the exploration of the effects of both relatively "soft" and "hard" metal ions, coordinated at a known position, on the chemical and physical properties of nucleotides and coenzymes. Specific interactions which will be investigated include: 1) the effect of the metal ion on the cleavage of the base-sugar bond, 2) migration of the metal ion to adjacent sites on the perimeter of purine and pyrimidine rings, 3) the reactivity of metal-nucleotide complexes with selected enzymes, and 4) the effect of metal ion coordination on the folding of coenzymes. Since flavin coenzymes engage in electron transfer with metal ions in proteins, a series of stable metalloflavin complexes will also be investigated with regard to their electron properties. The charge-transfer absorption bands exhibited by purine and pyrimidine complexes with second-row transition elements will be utilized as probes into the electronic structure of these ligands. Since these bands are also a function of the mileu of the complex, they will additionally be employed to indicate the nature of the substrate's enzymic environment. Paramagnetic metal ions firmly bound to nucleotides and coenzymes will be employed as NMR probes into the interactions of these molecules with proteins. Substitutable metal ions should provide the means for fixing the substrate at the enzymic binding site and so provide a valuable aid for delving protein-nucleotide interactions by a variety of physical techniques.